Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene
Journal Article
·
· European Molecular Biology Organization Journal
OSTI ID:936522
In the protein 4.1R gene, alternative first exons splice differentially to alternative 3' splice sites far downstream in exon 2'/2 (E2'/2). We describe a novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the distal E2'/2 acceptor via two nested splicing reactions regulated by novel properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its consensus 5' donor to splice to the proximal E2'/2 acceptor. A long region of downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal 3' AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2 product. We mapped branch points for both intrasplicing reactions and demonstrated that mutation of the E1B 5' splice site or branchpoint abrogates intrasplicing. In the 4.1R gene, intrasplicing ultimately determines N-terminal protein structure and function. More generally, intrasplicing represents a new mechanism whereby alternative promoters can be coordinated with downstream alternative splicing.
- Research Organization:
- Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
- Sponsoring Organization:
- Life Sciences Division
- DOE Contract Number:
- AC02-05CH11231
- OSTI ID:
- 936522
- Report Number(s):
- LBNL-838E
- Journal Information:
- European Molecular Biology Organization Journal, Journal Name: European Molecular Biology Organization Journal Journal Issue: 1 Vol. 27
- Country of Publication:
- United States
- Language:
- English
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